Clinical validation of circulating GDF15/MIC-1 as a marker of response to docetaxel and survival in men with metastatic castration-resistant prostate cancer
Date
2024-06-01ICR Author
Author
Mahon, KL
Sutherland, SIM
Lin, HM
Stockler, MR
Gurney, H
Mallesara, G
Briscoe, K
Marx, G
Higano, CS
de Bono, JS
Chi, KN
Clark, G
Breit, SN
Brown, DA
Horvath, LG
Type
Journal Article
Metadata
Show full item recordAbstract
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Elevated circulating growth differentiation factor (GDF15/MIC‐1), interleukin 4 (IL4), and IL6 levels were associated with resistance to docetaxel in an exploratory cohort of men with metastatic castration‐resistant prostate cancer (mCRPC). This study aimed to establish level 2 evidence of cytokine biomarker utility in mCRPC.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>IntVal: Plasma samples at baseline (BL) and Day 21 docetaxel (<jats:italic>n</jats:italic> = 120). ExtVal: Serum samples at BL and Day 42 of docetaxel (<jats:italic>n</jats:italic> = 430). IL4, IL6, and GDF15 levels were measured by ELISA. Monocytes and dendritic cells were treated with 10% plasma from men with high or low GDF15 or recombinant GDF15.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>IntVal: Higher GDF15 levels at BL and Day 21 were associated with shorter overall survival (OS) (BL; <jats:italic>p</jats:italic> = 0.03 and Day 21; <jats:italic>p</jats:italic> = 0.004). IL4 and IL6 were not associated with outcomes. ExtVal: Higher GDF15 levels at BL and Day 42 predicted shorter OS (BL; <jats:italic>p</jats:italic> < 0.0001 and Day 42; <jats:italic>p</jats:italic> < 0.0001). Plasma from men with high GDF15 caused an increase in CD86 expression on monocytes (<jats:italic>p</jats:italic> = 0.03), but was not replicated by recombinant GDF15.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Elevated circulating GDF15 is associated with poor prognosis in men with mCRPC receiving docetaxel and may be a marker of changes in the innate immune system in response to docetaxel resistance. These findings provide a strong rationale to consider GDF15 as a biomarker to guide a therapeutic trial of drugs targeting the innate immune system in combination with docetaxel in mCRPC.</jats:p></jats:sec>
Collections
Subject
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Urology & Nephrology
biomarker
docetaxel
growth differentiation factor 15
metastatic castration-resistant prostate cancer
prognosis
therapeutic response
MACROPHAGE INHIBITORY CYTOKINE-1
PHASE-III TRIAL
PLUS PREDNISONE
DOUBLE-BLIND
OPEN-LABEL
PLACEBO
GROWTH
CHEMOTHERAPY
MITOXANTRONE
MULTICENTER
Research team
PrCa Targeted Therapy
Language
eng
Date accepted
2024-03-07
License start date
2024-06-01
Citation
Prostate, 2024, 84 (8), pp. 747 - 755
Publisher
WILEY